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氟化二烷基亚硝胺的体外代谢

In-vitro metabolism of fluorinated diakylnitrosamines.

作者信息

Janzowski C, Gottfried J, Pool B L, Eisenbrand G, Preussmann R

出版信息

IARC Sci Publ. 1982(41):517-24.

PMID:7141558
Abstract

To elucidate differences in metabolism caused by fluorination of NDEA and NDBA, these compounds and their fluorinated analogs (NDEA-F3, NDEA-F6, NDBA-F3, NDBA-F6 and NDBA-F1 4) were incubated with rat liver microsomal fractions. Aldehydes, nitrite and unchanged nitrosamines were determined. Additionally, the mutagenicity was investigated with a Salmonella/mammalian microsome assay. NDEA-F6 and NDBA-F1 4 were not appreciably metabolized and were not mutagenic. NDEA, NDEA-F3, NDBA, NDBA-F3 and NDBA-F6 were dealkylated and, to a lesser extent, denitrosated. Dealkylation at the fluorinated alkyl group was inhibited, especially in the case of NDEA-F3. Whereas NDEA, NDBA, NDBA-F3 and NDBA-F6 were clearly mutagenic, mutagenicity of NDEA-F3 was only marginal.

摘要

为阐明由NDEA和NDBA氟化导致的代谢差异，将这些化合物及其氟化类似物（NDEA-F3、NDEA-F6、NDBA-F3、NDBA-F6和NDBA-F14）与大鼠肝脏微粒体组分一起孵育。测定了醛、亚硝酸盐和未变化的亚硝胺。此外，用沙门氏菌/哺乳动物微粒体试验研究了致突变性。NDEA-F6和NDBA-F14未被明显代谢且无致突变性。NDEA、NDEA-F3、NDBA、NDBA-F3和NDBA-F6发生了脱烷基反应，且程度较轻地发生了脱亚硝基反应。氟化烷基的脱烷基反应受到抑制，尤其是在NDEA-F3的情况下。虽然NDEA、NDBA、NDBA-F3和NDBA-F6具有明显的致突变性，但NDEA-F3的致突变性很微弱。

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